Gene therapy research has involved children and adults as research subjects, but not fetuses. It is anticipated that with further advances in knowledge, research into fetal gene therapy will become feasible and worth pursuing. This project explores whether the current regulations for protecting research subjects will provide adequate protections and guidance for future research involving human prenatal gene therapy. It seeks to determine whether additions or other revisions to the regulations are needed to deal with the ethical issues that will be raised in protecting human subjects in such research. Examples of issues that will need to be addressed include the following: 1) The current regulations do not specify how risks and benefits should be balanced between the fetus and pregnant woman. Is there a need for new rules concerning weighing risks and benefits? 2) For certain types of research, the current regulations give children stronger protections than fetuses. Are these relatively weaker protections for fetuses appropriate in the context of gene transfer research, or should stronger protections be extended to them? 3) The fetuses who might be considered for prenatal gene transfer research will have serious genetic diseases. One of the options for women who are informed about such diagnoses will be termination of pregnancy. Should an offer to participate in prenatal gene transfer research be made before, or should it be made after, the woman has made a decision about termination of pregnancy? Alternatively, should this vary, depending on the nature of the particular research? 4) In what situations should the informed consent of the father be obtained for fetal gene transfer research, in addition to the informed consent of the mother? 5) How should the definition of "minimal risk" in the current regulations, which includes the concept of "risks ordinarily encountered in daily life", be interpreted when applied to fetal research subjects? These and other questions will be addressed by carrying out literature research and conceptual and ethical analysis. For each issue, the project will identify main alternative views and the pros and cons of each view. Proposals concerning how the regulations should be worded will be presented. The results of this research will be disseminated by publication of peer-reviewed journal articles and by distribution to research oversight bodies. PUBLIC HEALTH RELEVANCE: Gene therapy research seeks treatments for serious genetic diseases, and it promises to have a significant health impact for society. In the future, it is anticipated that research into human prenatal gene therapy will be feasible and important. This project seeks to improve the protections that will be provided to subjects of prenatal gene therapy research, thereby contributing to the ethical standards for such research.